Biological and Molecular Aspects of Gastroenteropancreatic Neuroendocrine Tumors

Abstract

Neuroendocrine tumors of the digestive tract are rare entities characterized by significant phenotype differences and traditionally considered to originate from cells of the diffuse endocrine system of the pancreas and gut. Two major categories with significant phenotype and clinical behavior differences are identified as well-differentiated and poorly differentiated tumors. Investigation on the molecular basis of tumor development points to an important role for the multiple endocrine neoplasia syndrome type-1 (MEN1) gene because of its frequent abnormality observed both in well-differentiated and poorly differentiated tumors. Other genes are possibly involved, though the available data need support from studies on larger series of tumors.

Circulating biomarkers in gastroenteropancreatic neuroendocrine tumours

“…Neuroendocrine tumours (NETs) derive from neuroendocrine cells (highly specialised cells with both neural and endocrine characteristics) that upon specific stimulation secrete hormones regulating various functions (Rindi et al 2000). The various cell types of the neuroendocrine cell system can secrete products, such as peptides and biogenic amines that are tumour specific and may serve as markers for the diagnosis and follow-up of treatment.…”

“…The various cell types of the neuroendocrine cell system can secrete products, such as peptides and biogenic amines that are tumour specific and may serve as markers for the diagnosis and follow-up of treatment. Some tumour markers may have prognostic implications (Rindi et al 2000, Turner et al 2006, Vinik et al 2009). Neuroendocrine cells can be confined to a specific gland, such as the adrenal medulla (phaeochromocytomas) or the thyroid (medullary thyroid carcinoma).…”

“…The clinical presentation of gastroenteropancreatic neuroendocrine tumours (GEP-NETs) varies according to the site and size of the primary tumour, the presence or absence of metastatic spread, whether associated features compatible with a hereditary syndrome exist or not, whether the tumour is functional or not and, if so, what syndrome is present (Rindi et al 2000, Metz & Jensen 2008, Vinik et al 2009). Early on in the disease process, patients present with vague symptoms associated with various hormonal symptoms that often are misdiagnosed for many years.…”

The prognostic role of WHO classification, urinary 5-hydroxyindoleacetic acid and liver function tests in metastatic neuroendocrine carcinomas of the gastroenteropancreatic tract

“…Intracellular structure is characterised by cytoplasmic electron-dense granules and immunohistochemistry shows the expression of antigens commonly found in nerve elements (e.g. chromogranin A (CgA), NSE, synaptophysin, PGP 9.5) (Rindi et al, 2000;Rindi and Kloppel, 2004). Diffuse endocrine system of gastroenteropancreatic (GEP) tract represents the largest portion with at least 15 different types of neuroendocrine cells identified.…”

2 History and Physical Examination

“…19 Synaptophysin and chromogranin stains are highly sensitive and specific for NETs but cannot differentiate between subtypes. [20][21][22] Another helpful marker, serum chromogranin-A, is usually elevated in VIPomas but cannot differentiate between other NET subtypes. 23 Specific stains for VIP are not widely available and clinical correlation is mandatory.…”